Our enthusiasm for this project reflects our commitment to Mongolian public health sector development as well as our sense of urgency to resolve the vitamin D crisis and tuberculosis in Mongolia. My immediate and long term goals are to broaden my expertise in global health and nutritional epidemiology. With this award I intend to successfully complete the proposed aims and begin to establish myself as a global health professional with a focus in nutrition-related disease prevention. I plan to take formal course works, interact regularly with my mentors with formal evaluations of the progress and attend national meetings annually. Tuberculosis is predicted to be the largest single infectious cause of death between 1990 and 2020. More than 95% of the estimated TB cases and deaths due to TB occur in developing countries. We propose to examine the inter-relationships of nutrition, immunology, and epidemiology with respect to TB in Mongolia. Specifically, we propose a pilot study to test the effect of a daily vitamin D supplementation on the ability of subjects to control TB infection. We will also perform corollary studies on the effect of vitamin D supplementation on immune parameters. Aim 1: A. To recruit subjects, obtain consent, distribute vitamin D supplements to the children in the schools, obtain biologic specimens and to transport those specimens intact back to the United States. B. To test the hypothesis that daily vitamin D supplementation will increase plasma levels of 25(OH) D, and restore TLR-induced antimicrobial activity in monocytes/macrophages tested in vitro. Aim 2: To determine the efficacy of vitamin D supplement as an adjunct to multi drug therapy in enhancing the anti-microbial immune response to TB. Bacteriologic cure after the start of vitamin D therapy will be determined by ascertaining conversion of sputum culture to negative. The clinical outcomes include sputum culture conversion, relapse, or death. Cell-mediated immune endpoints will be measured including CD4+, CD8+, and CD3+ cell counts; ex vivo lymphocyte proliferation; and cytokine production. Relevance: Tuberculosis is one of the priorities in global health. Vitamin D deficiency is prevalent almost everywhere, both in developed and developing countries, the full potential of vitamin D is unknown but positive results would mean an inexpensive, non-toxic means, with possible other health benefits, to control a major killer in the world.